This program project has as its goal an increase in the understanding of mechanisms responsible for hypertension. Although emphasis was placed originally on the characterisics of the vascular changes we are now investigating more broadly all functional and structural changes that occur during evolution of hypertension. The principal experimental model we use is desoxycorticosterone acetate (DOCA) hypertension in young pigs (20 to 80 kg). Hemodynamic, endocrine and vascular reactivity studies have been carried out along with measurements of water and electrolyte balances. Evidence from these studies has supported the hypothesis that DOCA plus salt causes the resetting of a pressure regulating center. We will study this possibility by techniques giving chronic access to cerebrospinal fluid and by observing the effects of DOCA on anephric pigs maintained on dialysis. Vascular ultrastructure, vascular compliance and renin synthesis are also being studied.